O fator neurotrófico derivado do cérebro (BDNF) tem sido associado com a angiogênese por meio do seu receptor específico tropomiosina quinase B (TrkB). Uma vez que ambos são expressos em células endoteliais vasculares e o treinamento físico aeróbio (TF) pode aumentar os níveis séricos de BDNF, este estudo teve como objetivo testar as hipóteses de que: 1) Os níveis séricos de BDNF modulam o fluxo de sangue periférico; e 2) A presença do alelo Met no polimorfismo BDNF Val66Met prejudica o ganho de vasodilatação por TF. Foram genotipados para o polimorfismo do gene BDNF 304 voluntários saudáveis do sexo masculino (Val66Val, n = 221; Val66Met, n = 83) que foram submetidos a intenso TF em uma pista de corrida 3 vezes/semana durante 4 meses. Foram avaliados pré e pós-TF as concentrações circulantes de BDNF e pró-BDNF (ELISA), frequência cardíaca (FC), pressão arterial média (PAM), o fluxo de sangue do antebraço (FSA) e resistência vascular periférica (RVP). No período pré-TF, BDNF, pró-BDNF, a razão BDNF/pró-BDNF, FSA e RVP foram semelhantes entre todos os genótipos. Depois do TF, a capacidade funcional (VO2pico) aumentou e houve a diminuição da FC de repouso de forma semelhante em ambos os grupos. O grupo Val66Val, mas não o Val66Met, aumentou os níveis de BDNF (interação, p=0,04) e aumentou a razão BDNF/pró-BDNF (interação, p < 0,001). Curiosamente, as respostas do FSA (Interação, p=0,04) e da RVP (Interação, p=0,01), durante o exercício handgrip, do grupo Val66Val, apresentou melhoras quando comparado com o grupo Val66Met, mesmo com respostas similares de FC e PAM. Outras análises mostraram associação entre a razão BDNF/pró-BDNF e FSA (R=0,64; p < 0,001) e RVP (R=-0,58; p < 0,001). Estes resultados mostram que, em resposta ao TF, tanto a reatividade vascular periférica quanto o BDNF circulante são prejudicados pela presença do polimorfismo Val66Met do gene BDNF e esta responsividade está associada às concentrações de BDNF sérico em indivíduos saudáveis / The neurotrophin Brain-derived neurotrophic factor (BDNF) has been associated with angiogenesis through its specific receptor tropomyosin-related kinase B (TrkB). Since both are expressed in vascular endothelial cells and aerobic training (ET) can increase serum BDNF levels, this study aimed to test the hypotheses that: 1) Serum BDNF levels modulate peripheral blood flow; and 2) The presence of the allele Met in the BDNF Val66Met polymorphism impairs vasodilation gain by ET. We genotyped for BDNF polymorphism 304 healthy male volunteers (Val66Val, n= 221; Val66Met, n=83) which underwent to intense aerobic ET on a running track 3 times/week for 4 months. We evaluated pre and post ET serum BDNF and proBDNF concentration (ELISA), heart rate (HR), mean blood pressure (MBP), forearm blood flow (FBF) and forearm vascular resistance (FVR). In the pre ET, BDNF, proBDNF, BDNF/proBDNF ratio, FBF and FVR were similar between all genotypes. After ET, functional capacity (VO2peak) increased and HR decreased similarly in both groups. Val66Val, but not Val66Met, increased BDNF (Interaction, p= 0.04) and BDNF/proBDNF ratio (Interaction, p < 0.001). Interestingly, FBF (Interaction, p=0.04) and the FVR (Interaction, p=0.01) responses during handgrip exercise improved in Val66Val compared with Val66Met, even with similar responses of HR and MBP. Further analyses showed association between BDNF/proBDNF ratio and FBF (R=0.64, p < 0.001) and FVR (R=-0.56, p < 0001). These results show that peripheral vascular reactivity and serum BDNF responses to ET are impaired by the BDNF Val66Met polymorphism and such responsiveness is associated to the serum BDNF concentrations in healthy subjects

O fator neurotrófico derivado do cérebro (BDNF) tem sido associado com a angiogênese por meio do seu receptor específico tropomiosina quinase B (TrkB). Uma vez que ambos são expressos em células endoteliais vasculares e o treinamento físico aeróbio (TF) pode aumentar os níveis séricos de BDNF, este estudo teve como objetivo testar as hipóteses de que: 1) Os níveis séricos de BDNF modulam o fluxo de sangue periférico; e 2) A presença do alelo Met no polimorfismo BDNF Val66Met prejudica o ganho de vasodilatação por TF. Foram genotipados para o polimorfismo do gene BDNF 304 voluntários saudáveis do sexo masculino (Val66Val, n = 221; Val66Met, n = 83) que foram submetidos a intenso TF em uma pista de corrida 3 vezes/semana durante 4 meses. Foram avaliados pré e pós-TF as concentrações circulantes de BDNF e pró-BDNF (ELISA), frequência cardíaca (FC), pressão arterial média (PAM), o fluxo de sangue do antebraço (FSA) e resistência vascular periférica (RVP). No período pré-TF, BDNF, pró-BDNF, a razão BDNF/pró-BDNF, FSA e RVP foram semelhantes entre todos os genótipos. Depois do TF, a capacidade funcional (VO2pico) aumentou e houve a diminuição da FC de repouso de forma semelhante em ambos os grupos. O grupo Val66Val, mas não o Val66Met, aumentou os níveis de BDNF (interação, p=0,04) e aumentou a razão BDNF/pró-BDNF (interação, p < 0,001). Curiosamente, as respostas do FSA (Interação, p=0,04) e da RVP (Interação, p=0,01), durante o exercício handgrip, do grupo Val66Val, apresentou melhoras quando comparado com o grupo Val66Met, mesmo com respostas similares de FC e PAM. Outras análises mostraram associação entre a razão BDNF/pró-BDNF e FSA (R=0,64; p < 0,001) e RVP (R=-0,58; p < 0,001). Estes resultados mostram que, em resposta ao TF, tanto a reatividade vascular periférica quanto o BDNF circulante são prejudicados pela presença do polimorfismo Val66Met do gene BDNF e esta responsividade está associada às concentrações de BDNF sérico em indivíduos saudáveis / The neurotrophin Brain-derived neurotrophic factor (BDNF) has been associated with angiogenesis through its specific receptor tropomyosin-related kinase B (TrkB). Since both are expressed in vascular endothelial cells and aerobic training (ET) can increase serum BDNF levels, this study aimed to test the hypotheses that: 1) Serum BDNF levels modulate peripheral blood flow; and 2) The presence of the allele Met in the BDNF Val66Met polymorphism impairs vasodilation gain by ET. We genotyped for BDNF polymorphism 304 healthy male volunteers (Val66Val, n= 221; Val66Met, n=83) which underwent to intense aerobic ET on a running track 3 times/week for 4 months. We evaluated pre and post ET serum BDNF and proBDNF concentration (ELISA), heart rate (HR), mean blood pressure (MBP), forearm blood flow (FBF) and forearm vascular resistance (FVR). In the pre ET, BDNF, proBDNF, BDNF/proBDNF ratio, FBF and FVR were similar between all genotypes. After ET, functional capacity (VO2peak) increased and HR decreased similarly in both groups. Val66Val, but not Val66Met, increased BDNF (Interaction, p= 0.04) and BDNF/proBDNF ratio (Interaction, p < 0.001). Interestingly, FBF (Interaction, p=0.04) and the FVR (Interaction, p=0.01) responses during handgrip exercise improved in Val66Val compared with Val66Met, even with similar responses of HR and MBP. Further analyses showed association between BDNF/proBDNF ratio and FBF (R=0.64, p < 0.001) and FVR (R=-0.56, p < 0001). These results show that peripheral vascular reactivity and serum BDNF responses to ET are impaired by the BDNF Val66Met polymorphism and such responsiveness is associated to the serum BDNF concentrations in healthy subjects

Made available in DSpace on 2016-03-22T17:27:35Z (GMT). No. of bitstreams: 1 FERNANDAPEDROTTI_MESTRADO.pdf: 708081 bytes, checksum: 5ee01fbf7025bcd8bfa8448519f5340e (MD5) Previous issue date: 2014-11-13 / Background: Generalized Anxiety Disorder (GAD) is a common psychiatric disorder characterized by long term worry, tension, nervousness, fidgeting and symptoms of autonomic system hyperactivity. The neurobiology of this disorder is still unclear, although it has been consistently demonstrated that the environment and the genetic profile could increase its risk. We examined whether a polymorphism in the BDNF gene, which plays a role in neuroplasticity and memory, could increase the vulnerability to this disorder. Methods: In our study, 816 subjects from a population-based study were genotyped by qPCR for the BDNF functional variant rs6265 (Val66Met) and the BDNF serum levels were measured by ELISA. Results: Our results revealed a significant association between the Met allele and risk for GAD (p=0.014), but no differences were observed in the serum levels of BDNF according to diagnosis (p=0.531) or genotype distribution (p=0.197). The interaction between Val66Met genotype and GAD in explaining serum BDNF levels approached significance (F=3.93; p=0.048). The logistic regression analysis confirmed the independent association of Met allele as a risk factor to develop GAD after adjusting for confounders (&#946;=1.92; 95% IC: 1.168-3.16; p=0.010. Conclusion: These results suggest that BDNF could be involved in the neurobiology of GAD and might represent a useful marker associated with the disease. Key words: Anxiety disorders, generalized anxiety disorder, brain-derived neurotrophic factor, BDNF serum levels, Val66Met polymorphism / O transtorno de ansiedade generalizada (TAG) é uma doença crônica, caracterizada pelo excesso de ansiedade e preocupação somada à presença de outros sintomas, como tensão muscular, e irritabilidade (Hanrahan et al, 2013; Zargar et al, 2013). De acordo com o Manual Diagnóstico e Estatístico de Transtornos Mentais (DSM-IV), esse transtorno normalmente inicia na adolescência e afeta cerca de 5,7% da população em geral com altas taxas de incidência em mulheres (Kessler et al, 2005; Tempesta et al, 2013). Além disso, o TAG tem considerável impacto na qualidade de vida, sendo responsável por prejuízos na vida social, profissional e familiar dos seus portadores (Zargar et al, 2013; Tempesta et al, 2013). O TAG, geralmente é acompanhado de comorbidades psiquiátricas como a depressão maior, outros transtornos de ansiedade, e abuso de álcool, sendo caracterizado por altas taxas de falha na terapêutica, o que dificulta a resposta ao tratamento, bem como a resposta a psicoterapia (Zargar et al, 2013; Grant et al, 2005). O TAG é uma doença complexa na qual ocorre a interação de múltiplos fatores ambientais, biológicos e genéticos, cuja neurobilogia exata permanece ainda desconhecida (Zargar et al, 2013; Chen et al, 2006). O fator neurotrófico derivado do cérebro (BDNF), membro da família das neurotrofinas, age sobre certos neurônios do SNC e periférico, desempenhando um papel importante na sobrevivência, diferenciação e crescimento neuronal durante o desenvolvimento e na idade adulta (Gratacos et al, 2007; Egan et al, 2004). No cérebro está presente em regiões específicas como hipocampo, neocortex e hipotálamo, regiões-chave na regulação do humor e comportamento, bem como na aprendizagem e memória, indicando um envolvimento direto na patofisiologia das doenças psiquiátricas (Yoshii and Constantine-Paton, 2010; Lu et al, 2008). Estudos clínicos e pré-clínicos com transtornos de ansiedade demonstram que alterações no gene e nos níves de BDNF podem estar associados a doença (Hartmann et al., 2001; Rasmusson et al., 2002; Molle et al., 2012). Porém os estudos nesta área são escassos e inconsistentes, mas indicam que indivíduos com TAG apresentam uma maior frequência do alelo Met (Suliman et al, 2013; Ball et al, 2013). Dessa forma, uma melhor compreensão de alguns fatores genéticos envolvidos nos transtornos de ansiedade poderá permitir avanços não só ao nível de tratamento, mas também de prevenção e diagnóstico, podendo algumas alterações neurobiológicas vir a integrar os critérios de diagnóstico e monitoramento da doença, hoje exclusivamente semiológicos, e contribuir, assim, para a explicação da heterogeneidade desta patologia

Mental health has become a prominent issue in society. Yet, much remains unknown about the etiology of psychiatric disorders. The aim of the present thesis was to investigate the association between biological, psychological and social factors of risk and resilience and behavioral problems in a birth cohort of Swedish children. 1723 mothers and their children were followed from birth to the age of 12 as part of the South East Sweden Birth Cohort Study (the SESBiC study). Information was gathered through register data, standardized questionnaires and DNA samples. In study I, stability of maternal symptoms of depression and the impact on child behavior at age 12 were investigated. The prevalence of depressive symptoms was found to be 12.0 % postpartum. Symptoms of postpartum depression significantly increased the risk for subsequent depressive symptoms 12 years later in women. Children whose mothers reported concurrent symptoms of depression and anxiety had an increased risk for both internalizing and externalizing problems at age 12, but no long term effect on child behavior was seen for postpartum depressive symptoms. The greatest risk was seen for children whose mothers reported symptoms of depression on both occasions. In study II, the impact of gene-environment interaction of 5-HTTLPR and BDNF Val66Met and experience of life events together with symptoms of maternal depression and anxiety on child behavior at age 12 was studied. A main effect of 5-HTTLPR was noticed, but no geneenvironment effects were shown. Similarly to study I, concurrent symptoms of maternal depression and anxiety were an important predictor of child behavioral problems. A high degree of psychosocial stress around childbirth was found to have long lasting detrimental effects on child behavior, increasing the risk for internalizing problems at age 12. Study III investigated the impact of geneenvironment interactions of 5-HTTLPR and BDNF Val66Met and life events together with symptoms of maternal depression and birth characteristics on behavioral problems at age 3. Symptoms of postpartum depression were found to predict internalizing as well as externalizing problems in children three years later. Child experience of life events was a stable predictor of behavioral problems across the scales similar to sociodemographic factors such as parental immigration status and unemployment. No gene-environment interaction effects of 5-HTTLPR or BDNF Val66Met were shown. Study IV used the risk factors identified in studies I-III to investigate factors of resilience to behavioral problems at age 12. The l/l genotype of 5-HTTLPR was associated with a lower risk for behavioral problems at age 12, especially for children facing low adversity. Good social functioning was found to be a general resource factor, independent of the level of risk, while an easy temperament was associated with resilience for children with a high degree of adversity. However, effect sizes were small. In summary, the results from the present thesis emphasize the importance of maternal mental health and sociodemographic factors for child mental health at ages 3 and 12, which must be taken into account in clinical settings. Moreover, it adds to the null-findings of the gene-environment effect of 5-HTTLPR and BDNF Val66Met on behavioral problems in children, but indicates a main effect of 5-HTTLPR on internalizing symptoms at age 12.

Olfactory function is affected by demographic, cognitive, and genetic factors. In the present thesis, three empirical studies investigated individual differences in olfactory ability. Study I explored demographic and cognitive correlates in common olfactory tasks; odor detection, odor discrimination, and odor identification. The results indicated that old age influenced performance negatively in all tasks, and that semantic memory proficiency and executive functioning were related to odor discrimination and odor identification performance. No cognitive influence was observed for measurements of olfactory threshold. Using population-based data, Study II investigated a potential influence of the ApoE gene on olfactory identification after controlling for health status, semantic memory, and preclinical and clinical dementia. The main finding was that the ApoE- ɛ4 allele interacted with age, such that older ɛ4-carriers had an impaired odor identification performance relative to older non-carriers. Importantly, the negative ApoE- ɛ4 effect on olfactory proficiency was independent of clinical dementia conversion within five years. Study III investigated the effects of the BDNF val66met polymorphism on olfactory change over a five-year interval, in a community dwelling sample of young and old age cohorts. The results showed that age-related decline in olfactory identification was influenced by the BDNF val66met. In middle-aged subjects, no effect of BDNF val66met was observed although older val homozygote carriers showed a selectively larger olfactory decline than the older met carriers. Overall, results suggest that the relative influence of demographic and cognitive factors vary across different olfactory tasks and that two genes (ApoE and BDNF) impact age-related deficits in odor identification. Potential theoretical and practical implications of the findings are discussed as well as potential limitations of association studies in genomics research.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-03-31T23:30:54Z No. of bitstreams: 1 FernandaCarvalhoCagni_DISSERT.pdf: 1786366 bytes, checksum: c9744d9e47a1b28a2acd8f572b07d5da (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-04-05T20:01:37Z (GMT) No. of bitstreams: 1 FernandaCarvalhoCagni_DISSERT.pdf: 1786366 bytes, checksum: c9744d9e47a1b28a2acd8f572b07d5da (MD5) / Made available in DSpace on 2016-04-05T20:01:37Z (GMT). No. of bitstreams: 1 FernandaCarvalhoCagni_DISSERT.pdf: 1786366 bytes, checksum: c9744d9e47a1b28a2acd8f572b07d5da (MD5) Previous issue date: 2015-05-12 / As doen?as neurodegenerativas s?o objeto frequente de estudo devido ao n?mero crescente de casos associados ao processo de envelhecimento populacional e pelo impacto que causam na qualidade de vida dos indiv?duos. A doen?a de Parkinson (DP) ? a segunda doen?a neurodegenerativa mais frequente. Apesar da sua etiologia ainda n?o ser completamente conhecida, sabe-se que a mesma ? causada por fatores ambientais e gen?ticos. Assim, a investiga??o dos fatores etiol?gicos e os mecanismos respons?veis pelas altera??es que levam a DP podem contribuir para o seu diagn?stico e preven??o. Uma poss?vel associa??o entre DP e o polimorfismo comum do Fator Neurotr?fico Derivado do C?rebro (BDNF) G196A (Val66Met) tem sido sugerido por diferentes estudos com resultados contrastantes. Por esse motivo, o objetivo deste estudo ? verificar se o polimorfismo BDNF Val66Met confere susceptibilidade a DP em uma amostra de pacientes brasileiros e se isso implica em quaisquer altera??es no n?vel de BDNF em sangue total e na manifesta??o de sintomas. A amostra foi constitu?da de pacientes acompanhados pelo servi?o de neurologia do Hospital Universit?rio Onofre Lopes (HUOL) e controles saud?veis (CTRL). Os aspectos motores da DP foram avaliados pela Escala de Hoehn e Yahr (HY), Unified Parkinson?s Disease Rating Scale (UPDRS) e Escala de Atividades Di?rias de Schwab e England (SE). Para a avalia??o dos aspectos n?o-motores foram utilizados os instrumentos: Bateria de Avalia??o Frontal (BAF), Mini Exame do Estado Mental (MEEM), Invent?rio de Depress?o de Beck (IDB) e o Invent?rio de Ansiedade de Beck (IAB). Amostras de sangue foram coletadas para a genotipagem do polimorfismo Val66Met e mensura??o da concentra??o de BDNF em sangue total. Como esperado, os pacientes com DP apresentaram pior desempenho na avalia??o motora, cognitiva e emocional. A distribui??o dos alelos entre os grupos n?o foi significativamente diferente, por?m o gen?tipo A/G foi associado significativamente como protetor para a DP. O gen?tipo G/G, por sua vez, foi associado significativamente com o desenvolvimento de depress?o e ansiedade em pacientes com DP. No entanto, as concentra??es de BDNF n?o foram diferentes entre os gen?tipos ou grupos. Este ? o primeiro estudo de associa??o gen?tica desse polimorfismo com a DP no Brasil e o primeiro que associou o heterozigoto A/G com prote??o contra a DP. / Neurodegenerative diseases are frequently studied due to the increasing number of cases associated with the populational ageing and to the impact on the conditions on the quality of life. Parkinson?s disease (DP) is the second most frequent neurodegenerative disease. Despite the fact that its etiology is not completely understood, it is known that DP is caused by environmental and genetic factors. Thus, the investigation of etiologic factors and mechanisms responsible for the changes that lead to DP may help early diagnostic and prevention. A possible association between DP and the common polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies with contrasting results. For this reason, the aim of this study is to investigate if the BDNF Val66Met polymorphism is related to susceptibility to DP in a cohort of Brazilian patients. Additionaly, we verify if the presence of the polymorphism implies in alterations in the BDNF whole blood concentrations, as well as variations in symptomatology. The sample comprised Brazilian patients accompanied by the neurology service of the Onofre Lopes University Hospital (HUOL) and healthy controls (CTRL). The motor aspects of DP were evaluated by Hoehn e Yahr Scale (HY), Unified Parkinson?s Disease Rating Scale (UPDRS) and Schwab & England Scale (SE). For the evaluation of non-motor symptoms were used the following instruments: Frontal Assessment Battery (BAF), Mini-Mental State Examination (MEEM), Beck Depression Inventory (IDB) and the Beck Anxiety Inventory (IAB). Blood samples were collected for BDNF Val66Met polymorphism genotyping and BDNF whole blood measurement. As expected, DP patients performed worse in motor, cognitive and emotional battery of questionnaires. Alleles distribution between DP and CTRL was not significantly different, but the A/G genotype was significantly associated with a protector factor for DP. In contrast, the G/G genotype was significantly associated with depression and anxiety development in DP patients. However, BDNF concentrations were not different between genotypes or groups. This is the first study of genetic association of this polymorphism with DP in Brazilian subjects and the first one that associate A/G genotype with protection against DP.

Affect and cognition have traditionally been considered mutually exclusive domains and their study has evolved into two separate research fields. In recent years, however, there is increasing evidence of affective modulations of cognitive processes and interest in the study of affective cognition has grown. This thesis presents analyses of data collected in four mixed-design experiments between 2009 and 2011, which were designed to investigate affective memory and its electrophysiological correlates, individual differences in said affective memory and electrophysiological correlates, the time-course of affective memory and attentional disengagement from affective stimuli respectively. The first aim of the research presented here was to further understanding of how affective content influences picture processing and memory. Event-related potentials (ERPs) provide a valuable tool for the investigation of modulations of cognitive processes, as their excellent temporal resolution allows for the dissociation between different processes contributing to behavioural outcomes. Several important results for the study of affective cognition are reported: The late positive potential (LPP) was shown to be modulated differentially by affective content when compared to a behavioural attentional disengagement task. While the behavioural measure of attention replicated findings from participants’ self-report of arousal, LPP enhancement did not. This novel finding demonstrates that the affective modulation of the LPP cannot be used as an electrophysiological marker of slowed attentional disengagement as is common in the literature. In the domain of recognition memory, affective modulation of performance was shown to be time-sensitive, with effects developing faster for negative than for positive picture content. Affective pictures were associated with a less conservative response bias than neutral pictures but only negative pictures elicited better discrimination performance, driven by an increased in the rate of “remembered” as compared to merely familiar pictures. This was reflected in an increase of the ERP old/new effect for negative pictures in the 500 to 800ms time window, the purported correlate of recollection. The late right-frontal old/new effect between 800 and 1500 ms post stimulus onset was shown to be attenuated by affective content, supporting the interpretation of the late right-frontal effect as a correlate of relevance detection over a retrieval success interpretation. In combination, the findings add weight to the conclusion that affective content enhances memory through selective memory sparing for affective stimuli. Novel evidence for gender differences in affective cognition was found. Comparisons between female and male participants revealed that the affective modulation of the late right-frontal effect differs between the genders, underlining the importance of assessing and understanding gender differences as part of the study of affective cognition. Brain-derived neurotrophic factor (BDNF) gene val66met single nucleotide polymorphism (SNP), a small genetic change that affects the functioning of BDNF, a protein that plays an important role in neuron growth, differentiation and survival, is shown here to also affect the interaction of affect and cognition. BDNF val66met genotype modulated the early “familiarity” old/new effect selectively in response to positive pictures. The present study clearly demonstrates the value of the ERP technique in the investigation of individual differences in affective and cognitive processing and the need to take such individual differences into account as part of the endeavour to fully understand the mechanisms of affective processing, cognition and affective cognition. A better understanding of the role of gender and genetic differences in the affective modulation of affective processing and memory will have important practical implications in fields where affect and cognition interact.

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Introdução: A religiosidade e espiritualidade (R/E) são aspectos importantes na vida e cultura de grande parte da população. Embora as práticas religiosas sejam universais e evidências demostrem sua importância clínica, as bases biológicas desse comportamento são pouco investigadas, particularmente a níveis genéticos. Objetivos: Verificar a associação dos polimorfismos 5-HTTLPR, SNP na região UTR 3’ (rs3813034) do gene 5-HTT, Val66Met do gene BDNF e repetições do éxon III do gene DRD4 com mediunidade e religiosidade/espiritualidade; além disso verificar a relação entre os polimorfismos gênicos de médiuns espíritas e grupo controle e traços de personalidade. Métodos: O estudo incluiu 130 voluntários, sendo 75 médiuns espíritas e 55 voluntários não médiuns do grupo controle. Foi distinguido os genótipos dos polimorfismos 5-HTTLPR, SNP rs3813034 do gene 5-HTT, Val66Met do gene BDNF e repetições do éxon III do gene DRD4. Os voluntários responderam questionários de Religiosidade P-DUREL, Inventário de Temperamento e Caráter de Cloninger (ITC) e Self-Report screening questionnaire (SRQ). Resultados: Amostras de médiuns espíritas tem alta religiosidade pela P-DUREL e altas pontuações nas dimensões de caráter do ITC comparadas ao grupo controle. Não houve diferença significativa entre SRQ+ de médiuns (20%) e grupo controle (26,8%). Não foi encontrado associação entre genótipos e mediunidade ou religiosidade pela P-DUREL. Houve associação entre os genótipos 5-HTTLPR, o SNP rs3813034 e repetições do gene DRD4 e subescalas da dimensão Autotranscendência (AT) de Cloninger. A subescala Identificação transpessoal se associou exclusivamente a genótipos de médiuns espíritas. Conclusão: Médiuns espíritas possuem personalidade associada a boa saúde mental e baixa prevalência de transtornos mentais. De acordo com os resultados obtidos há indicativo de que polimorfismos 5- HTTLPR, rs3813034 do gene 5-HTT e do DRD4 de médiuns afeta a dimensão de caráter autotranscendência da TCI. / Introduction: Religion and spirituality (R / E) are important aspects in the life and culture of a large part of the population. Although religious practices are universal and evidence demonstrates their clinical importance, the biological basis of such behavior is poorly investigated, particularly at genetic levels. Objectives: To verify the association of 5- HTTLPR, SNP polymorphisms in the 3 'UTR region (rs3813034) of the 5-HTT gene, Val66Met of the BDNF gene, and 48 bp repeats on exon III of the DRD4 gene with mediumship and religiosity / spirituality; In addition to verify the relationship between the gene polymorphisms of spiritist mediums and control group and personality traits. Methods: The study included 130 volunteers, 75 Spiritist mediums and 55 non-medium volunteers from the control group. Genotypes of the 5-HTTLPR polymorphisms, rs3813034 SNPs of the 5- HTT gene, Val66Met of the BDNF gene and exons of the exon III of the DRD4 gene were distinguished. The volunteers answered the following questionnaires: P-DUREL, Cloninger’s Temperament and Character Inventory (ITC) and Self-Report screening questionnaire (SRQ). Results: Spiritist mediums scored high religiosity in P-DUREL and high scores on the ITC’s character dimensions compared to the control group. There was no significant difference between SRQ + of mediums (20%) and control group (26.8%). There was no association between genotypes and mediumship or religiosity by P-DUREL. There was an association between the 5-HTTLPR genotypes, the rs3813034 SNP and DRD4 gene repetition and Cloninger's Autotranscendence (AT) subscales. The subscale Transpersonal Identification was exclusively associated with genotypes of spiritist mediums. Conclusion: Spiritist mediums have personality traits associated with good mental health and low prevalence of mental disorders. According to the results, there are indications that 5-HTTLPR and rs3813034 polymorphisms of the 5-HTT gene and the DRD4 can affect the character dimension of self-transcendence of the TCI when mediumship is present. / Tese (Doutorado)

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La présente thèse porte sur les effets à long terme des traumatismes craniocérébraux légers (TCCL), incluant les commotions cérébrales, ainsi que sur certains facteurs influençant l’évolution post-blessure chez deux populations considérées vulnérables, soit les athlètes féminines ainsi que les adultes vieillissants. Dans une première étude, les capacités olfactives d’athlètes féminines commotionnées, mais asymptomatiques, ont été évaluées en moyenne deux ans après la dernière commotion. L’intérêt de cette étude réside principalement dans l’investigation du rôle potentiel du polymorphisme BDNF Val66Met (BDNFMet), associé à une sécrétion réduite de la protéine BDNF impliquée dans la neuroplasticité, pour expliquer les variations du fonctionnement olfactif post-commotion. Dans une deuxième étude, les effets cognitifs d’avoir subi un seul TCCL ont été caractérisés chez des individus âgés de 50 à 70 ans ayant subi leur blessure environ cinq ans plus tôt. Cette caractérisation est particulièrement pertinente alors que la majorité des études s’intéressant aux effets à long terme de cette blessure ont étudié des individus ayant subi de multiples TCCL. De plus, cette étude visait à évaluer si un programme d’entraînement physique aérobie de douze semaines permettrait d’améliorer les fonctions cognitives altérées chez les TCCL comparativement aux contrôles. Les résultats de la présente thèse permettent d’abord de mieux caractériser certains effets à long terme du TCCL. Plus précisément, la première étude suggère un patron de fonctionnement olfactif distinct selon le génotype BDNF chez les athlètes féminines commotionnées. Ainsi, les porteuses du BDNFMet ont significativement mieux performé que les BDNFval aux différentes tâches olfactives. Puisque cette relation génétique n’était pas présente chez les participantes contrôles, ces résultats suggèrent que le fonctionnement olfactif, suite à une commotion cérébrale, est, du moins en partie, médié par le polymorphisme BDNFMet. La deuxième étude suggère, pour sa part, des effets cognitifs à long terme d’avoir subi un seul TCCL chez des individus sédentaires, mais en santé, âgés de 50 à 70 ans. Ainsi, les participants TCCL ont moins bien performé que les participants contrôles, appariés pour l’âge et le sexe, aux tâches neuropsychologiques mesurant des aspects de la vitesse de traitement de l’information, du fonctionnement exécutif (planification, fluence verbale) et de la mémoire visuelle. Cette étude n’a toutefois pas relevé de différence sur le plan de l’attention, de l’inhibition, de la mémoire verbale et des habiletés visuoconstructives. Ces résultats cognitifs sont un ajout intéressant à la littérature, car ils surviennent chez des individus qui ne présentaient aucun des facteurs de risque (maladie chronique, problème de santé mentale) typiquement associés aux effets à long terme des TCCL. En ce qui a trait au deuxième volet de l’étude, l’exercice physique aérobie a permis d’améliorer les capacités cardiorespiratoires (VO2max) des patients TCCL davantage que les étirements (condition contrôle). Toutefois, dans ce petit échantillon de seize participants, l’exercice aérobie n’a pas permis d’améliorer les fonctions cognitives altérées des patients TCCL. Différentes explications possibles sont abordées afin de guider les futures études. / The following thesis investigates the long-term effects of mild traumatic brain injury (mTBI), including concussions, and factors influencing post-injury evolution in two vulnerable populations: female athletes and aging individuals. In a first study, olfactory capacities of asymptomatic concussed female athletes were evaluated an average of two years after their last concussion. The appeal of this study lies mainly in its investigation of the potential role of the BDNF Val66Met (BDNFMet) polymorphism, which is associated with reduced secretion of the BDNF neuroplasticity protein, on post-concussion olfactory variations. In a second study, cognitive effects of sustaining a single mTBI were assessed in individuals between 50 and 70 years old who sustained their injury on average five years earlier. This characterization is particularly relevant given that most studies focusing on long-term effects of this injury have studied individuals having sustained multiple mTBI. Furthermore, this study also aimed to evaluate if a twelve-week aerobic exercise program would allow improvements of altered cognitive functions in mTBI patients. Results from the following thesis first allow to better describe some long-term effects of mTBI. More precisely, the first study suggests different patterns of olfactory functioning according to BDNF genotype in female concussed athletes. Thus, BDNFmet carriers performed significantly better than BDNFval carriers at the different olfactory tasks. Given that this genetic relationship was not present in control participants, these results suggest that olfactory functioning following a concussion is, at least in part, mediated by the BDNFmet polymorphism. As for the second study, it suggests long-term cognitive effects of having sustained a single mTBI in sedentary, but healthy, individuals between the ages of 50 and 70. Indeed, mTBI participants showed lower performance when compared to age and sex-matched control participants on neuropsychological tasks measuring aspects of processing speed, executive functioning (planning, verbal fluency) and visual memory. This study did not find any difference regarding attention, inhibition, verbal memory and visuoconstructive abilities. These cognitive results are an interesting contribution to the literature as they occur in individuals presenting no risk factor (chronic disease, mental health disorders) typically associated with long-term effects of mTBI. Regarding the second phase of this study, aerobic exercise improved cardiorespiratory fitness (VO2max) more than stretching (control condition) in mTBI patients. However, in this small sample of sixteen participants, aerobic exercise did not allow to improve altered cognitive functions in mTBI participants. Different possible explanations are addressed to guide future studies.